Project Summary. Access to enantioenriched molecules is crucial to modern biomedical research. Many of the most important reactions in organic synthesis rely on protonation as a key mechanistic step. As such, chiral Brnsted acid catalysis has emerged as a highly effective strategy for the production of valuable molecular building blocks in enantioenriched form. This area of catalysis has been dominated, however, by a very limited number of catalyst systems that are laborious, time-consuming, and expensive to prepare, a fact that greatly impedes new reaction discovery, development, and application. Thus, there exists a clear impetus for the invention of new enantioselective Brnsted acid catalysts with increased potency and effectiveness that are trivial to prepare and easy to modify. In addition, there is a strong expectation that fundamentally different catalyst structures will offer orthogonal reactivity patterns and thus enable the invention of new methods. Toward this end, we have developed a fundamentally new class of highly reactive and enantioselective Brnsted acid catalysts, based on pentacarboxycyclopentadienes (PCCPs). Notably, PCCPs are formally carbon acids with acidities that exceed many established catalytic platforms. Pentacarboxycyclopentadienes offer a number of compelling advantages including: (1) high acidity and reactivity; (2) extreme ease of preparation; (3) catalyst modularity; and (4) amenability to scale. Based on our initial investigations, we envision that PCCPs may emerge as a definitive platform for enantioselective Brnsted acid catalysis. In each of the projects targeted herein, we aim to apply PCCP catalysis to address a prominent challenge in organic synthesis. The asymmetric transformations targeted in this grant are either currently unknown or suffer from significant limitations of substrate scope. Among the specific reactions that we aim to develop in the context of this grant are: enantioselective Mukaiyama Mannich reactions with alkyl imines; nucleophilic additions to dihydropyrrolones; enolate additions to oxocarbenium ions; Gassman-Michael reactions; benzylic alcohol substitutions; dihydrobenzofuran acetal substitutions; substitutions via oxyallyl cations; and Gassman Diels- Alder reactions. The development of these proposed transformations and the further establishment of the PCCP catalyst platform will represent significant advances for the field of organic synthesis.